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Thromboelastography-based dynamic evaluation of perioperative coagulation changes and anticoagulant efficacy in lung cancer patients

Thrombosis Journal volume 23, Article number: 31 (2025) Cite this article

Abstract

Background

Venous thromboembolism (VTE) is a common postoperative complication in oncologic surgery, closely associated with perioperative hypercoagulability. Thromboelastography (TEG) may be an effective method for monitoring hypercoagulability and guiding preventive anticoagulation.

Methods

We prospectively collected perioperative clinical data from lung cancer surgery patients at our hospital between June 2019 and January 2020. TEG and coagulation-related indicators were monitored preoperatively, and on postoperative days 1 and 3. Newly diagnosed postoperative VTE was monitored using lower limb color doppler ultrasound.

Results

A total of 241 lung cancer surgery patients were included, with 25 developing VTE postoperatively (10.4%). TEG results showed a significant decrease in the R value (a thrombin marker) on postoperative day 1, followed by an increase on day 3. The MA value (a platelet marker) increased postoperatively. D-dimer levels also rose after surgery. On postoperative day 1, thrombin-related hypercoagulability was predominant (15/17 preoperatively, 40/46 postoperatively), whereas platelet-related hypercoagulability was dominant on postoperative day 3 (18/35). Patients who received prophylactic anticoagulation had significantly higher R values on day 3. The ROC curve for D-dimer predicting new-onset VTE showed AUCs of 0.732, 0.790, and 0.847 preoperatively, on days 1, and 3, respectively.

Conclusion

D-dimer helps identify high-risk patients for postoperative VTE, while TEG aids in classifying and monitoring hypercoagulability, optimizing anticoagulation therapy choices and dosages.

Introduction

Primary lung cancer is the second most common malignancy worldwide, yet it has the highest mortality rate among all cancers [1]. In recent years, due to advancements in treatment methods such as surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, the overall survival rate of lung cancer patients has significantly improved. At the same time, the risk of venous thromboembolism (VTE) in these patients has also increased [2,3,4]. Studies report that 7–15% of lung cancer patients develop VTE, with adenocarcinoma showing a 3- to 4-fold higher incidence of thrombosis compared to squamous cell carcinoma and small cell lung cancer [5,6,7]. Given this increasing risk, there is an urgent need to explore the mechanisms underlying VTE in lung cancer patients and optimize prevention and treatment strategies [5, 8].

To reduce the incidence of VTE, prophylactic anticoagulation therapy is typically administered to patients during the perioperative period in surgical procedures, with commonly used medications including low-molecular-weight heparin (LMWH) and other anticoagulants [9]. Clinical guidelines recommend extending prophylactic anticoagulation therapy to 28 days for patients undergoing cancer surgery to reduce the risk of postoperative VTE [10,11,12,13]. Although widely accepted and applied in clinical practice, this recommendation lacks strong evidence-based support. The guidelines are often based on limited data and do not fully account for the specific circumstances of different cancer types, the extent of surgical trauma, variations in patient coagulation function, or individualized VTE risk. Additionally, anticoagulant therapy is not without risks. Excessive anticoagulation may lead to bleeding complications, with the perioperative period carrying an even higher risk of hemorrhage [13]. Therefore, balancing the benefits of anticoagulation with the potential risks is one of the key challenges faced by clinicians in practice.

Thromboelastography (TEG) is a non-invasive, in vitro coagulation function test that evaluates the dynamic changes in the viscoelastic properties of a blood sample as it clots under moderate shear stress. TEG provides a comprehensive real-time functional assessment of the entire coagulation cascade, from the initial platelet-fibrin interaction, through platelet aggregation, clot strengthening, fibrin cross-linking, and finally fibrinolysis. This allows clinicians to obtain detailed information about a patient’s coagulation status [14]. In perioperative management, TEG not only helps assess the patient’s baseline coagulation status but also allows for individualized adjustments to anticoagulant therapy based on the risk of hypercoagulability [15, 16]. Additionally, TEG can dynamically monitor the effectiveness of anticoagulation treatment during therapy, ensuring both its efficacy and safety [17, 18].

In this study, we aim to monitor and classify the perioperative hypercoagulable state in lung cancer patients using TEG, providing guidance for the selection and timing of prophylactic anticoagulant therapy. By dynamically assessing the effectiveness of standard anticoagulation treatment through TEG, we aim to offer insights for personalized anticoagulation strategies, optimizing treatment and reducing the risk of VTE.

Materials and methods

Study population

We prospectively collected data from patients who underwent radical lung cancer surgery at our hospital between June 2019 and January 2020. The inclusion criteria are as follows: (1) age 18 to 75, no gender restriction; (2) preoperative evaluation indicated no contraindication to surgery; (3) no anticoagulation or antiplatelet therapy within 30 days before surgery; (4) patients and their family members agreed with the protocol and signed the informed consent form.

The exclusion criteria are as follows: (1) preoperative examination revealed the presence of VTE; (2) distant metastasis was detected during surgery and radical surgery was abandoned; (3) the presence of hematological diseases or other systemic malignancies; (4) insufficient follow-up information.

Perioperative management

All patients underwent color Doppler ultrasound of both lower limbs before surgery and prior to discharge to determine the presence of any new postoperative deep vein thrombosis (DVT). If any of the following conditions were present, computed tomography pulmonary angiography (CTPA) was performed to rule out new-onset pulmonary embolism (PE): typical symptoms of PE, such as chest pain, hemoptysis, or unexplained hypoxemia and dyspnea; newly developed DVT after surgery.

For patients classified as high risk based on the modified Caprini score [19], prophylactic anticoagulation should be administered if there is no significant risk of postoperative bleeding. Typically, low-molecular-weight heparin (LMWH) (e.g., nadroparin calcium) is administered starting from the evening of the first postoperative day, with a dose ranging from 0.3 to 0.6 ml depending on the patient’s weight, continuing until discharge.

Clinical data collection

We collected relevant patient data through the electronic medical record system, including basic information (height, weight, age, gender, etc.), comorbidities (such as hypertension, diabetes, coronary heart disease, etc.), surgical information (surgical approach, resection scope, surgery duration), pathological results (pathological type, differentiation grade), laboratory test results (platelet count, PT, APTT, INR, D-dimer, etc.), and whether new postoperative VTE events occurred. All patients underwent routine coagulation tests and TEG on the day before surgery, as well as on the 1st and 3rd days postoperatively, to assess the dynamic changes in coagulation status during the perioperative period.

The main parameters monitored by TEG include the reaction time (R value), which represents the time from the start of the test to the formation of the clot, reflecting thrombin generation; maximum amplitude (MA), which indicates the maximum strength and stability of the clot, primarily representing the interaction between platelets and fibrin; the angle (α angle), which measures the speed of clot propagation, indicating the rate of platelet aggregation and fibrin cross-linking; kinetics (K value), which reflects the speed of clot formation; and clot lysis at 30 min (LY30), which evaluates fibrinolysis 30 min after the clot has reached its maximum amplitude (MA). Additionally, TEG provides a clotting index (CI), which is based on the above four parameters and used to assess overall coagulation status. The hypercoagulability can be categorized into three types based on TEG: (1) thrombin-related hypercoagulability, defined as CI > 3, R ≤ 5 min, and MA ≤ 70 mm; (2) platelet-related hypercoagulability, defined as CI > 3, R > 5 min, and MA > 70 mm; and (3) mixed hypercoagulability, defined as CI > 3, R ≤ 5 min, and MA > 70 mm [20].

Statistical analysis

Measurement data following a normal distribution are expressed as mean ± standard deviation, while non-normally distributed data are represented as median (interquartile range). Quantitative data are presented as numbers (percentages). For normally distributed data, a t-test is used to compare between groups; for non-normally distributed data, the rank-sum test is applied. Categorical data are compared using the chi-square test. The measurement data for each patient at various time points were statistically analyzed using repeated measures ANOVA. The predictive performance of biomarkers for VTE is evaluated using ROC curve analysis, with statistical significance set at P < 0.05. Data analysis is conducted using SPSS version 24.0 and GraphPad Prism version 8.0.

Results

The baseline information of lung cancer patients

A total of 241 patients were included in this study, of which 25 experienced VTE events postoperatively, with an incidence rate of 10.4%. Based on the occurrence of VTE, all patients were divided into two groups: the VTE group and the non-VTE group. Through group comparisons, we found statistically significant differences between the two groups in terms of age (64.4 ± 8.2 vs. 58.4 ± 10.0), operation duration (152.6 ± 67.0 vs. 125.5 ± 45.3), surgical method (VATS) (76.0% vs. 90.3%), surgical procedure, preoperative D-dimer (0.41 vs. 0.19), and preoperative R values (6.4 ± 1.7 vs. 7.1 ± 1.4) (P < 0.05) (Table 1).

Table 1 The baseline information of lung cancer patients in this study
Full size table

Dynamic changes in coagulation status during the perioperative period

We conducted TEG, coagulation function tests, and routine blood tests for all patients during the perioperative period (preoperatively, on postoperative day 1 and day 3). Relevant indicators were recorded for both the VTE group and the non-VTE group, and a comparative analysis was performed to assess the dynamic changes of these indicators during the perioperative period and their potential predictive role in VTE occurrence.

In the TEG-related indicators, the R value in the VTE group was lower than that in the non-VTE group at all perioperative time points, with a statistically significant difference observed preoperatively. In the repeated measures ANOVA, statistically significant differences were observed in the R values across all time points (6.9 ± 1.5, 6.1 ± 1.3, 6.3 ± 1.1; P < 0.05), indicating that the values changed significantly over time. The MA value in the VTE group was higher than that in the non-VTE group at all perioperative time points, though this difference was not statistically significant. There were also no significant differences between the two groups in angle and k values (Fig. 1A-D).

Fig. 1
figure 1

The dynamic changes of coagulation-related indicators during the perioperative period. D: Respectively represent the dynamic changes of R, MA, Angle, and k values in the TEG; E-F: Respectively represent the dynamic changes of APTT, INR, D-dimer, and PLT in routine coagulation tests

Full size image

In the routine coagulation indicators, D-dimer levels in the VTE group were higher than those in the non-VTE group at all perioperative time points, with statistically significant differences on postoperative day 1 and day 3. The other indicators showed no significant differences (Fig. 1E-H).

Identify hypercoagulability and monitor anticoagulant effectiveness

We used TEG to identify perioperative hypercoagulability and monitor the effectiveness of prophylactic anticoagulation. The results showed that preoperatively, 17 patients (17/241, 7.1%) were in a hypercoagulable state, with 15 exhibiting thrombin-related hypercoagulability, 1 with platelet-related hypercoagulability, and 1 with a mixed hypercoagulability. On postoperative day 1, 46 patients (46/241, 19.1%) were in a hypercoagulable state, including 40 with thrombin-related hypercoagulability, 3 with platelet-related hypercoagulability, and 3 with a mixed hypercoagulability. On postoperative day 3, 35 patients (35/241, 14.5%) were in a hypercoagulable state, with 14 showing thrombin-related hypercoagulability, 18 with platelet-related hypercoagulability, and 3 with a mixed hypercoagulability (Fig. 2).

Fig. 2
figure 2

The change in the number of patients with perioperative hypercoagulability and their specific classifications

Full size image

In this study, a total of 51 patients received postoperative prophylactic anticoagulation, which was administered from the night of the postoperative day 1 until discharge. We monitored the effectiveness of anticoagulation by observing changes in the R value in TEG. Results showed no significant difference in the R value between the anticoagulation and non-anticoagulation groups on the postoperative day 1, but on the postoperative day 3, the R value in the anticoagulation group was significantly higher than that in the non-anticoagulation group (Fig. 3A). For patients receiving prophylactic anticoagulation, anticoagulant therapy resulted in an increase in the R value, but this difference was not statistically significant (Fig. 3B).

Fig. 3
figure 3

Perioperative dynamic changes in R value for patients (anticoagulation group vs. non-anticoagulation group). A: The specific value changes of R value during the perioperative period; B: Changes in R value before and after prophylactic anticoagulation

Full size image

Biomarkers predicting postoperative VTE

We used ROC curve analysis to evaluate the utility of these biomarkers in predicting VTE. The results showed that R and MA had limited roles in predicting VTE, while D-dimer demonstrated significant clinical value. The ROC curve for D-dimer predicting new-onset VTE showed AUCs of 0.732, 0.790, and 0.847 preoperatively, on day 1, and day 3, respectively (Fig. 4).

Fig. 4
figure 4

ROC curve for biomarkers predicting postoperative VTE in lung cancer. A-C: Represent the ROC curves of perioperative R, MA, and D-dimer in predicting VTE, respectively

Full size image

Discussion

VTE primarily includes deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT most commonly occurs in the veins of the legs but can also occur in the cerebral, visceral, and arm veins. VTE is a multifactorial disease caused by the interaction or accumulation of various triggers, with primary factors including major surgery, prolonged bed rest, and active cancer [21,22,23]. A common complication of VTE is postthrombotic syndrome, a collection of signs and symptoms associated with chronic venous insufficiency [24]. This condition can cause discomfort, including joint swelling, leg ulcers, and limping, which not only reduces quality of life but also imposes a significant economic and healthcare burden [24, 25]. Patients undergoing surgery for lung tumors are among the highest-risk groups for postoperative VTE [13]. Perioperative hypercoagulability is a major contributing factor to the occurrence of VTE, and low molecular weight heparin (LMWH) is an important treatment choice to address this condition [26]. However, there is a lack of effective methods to evaluate both hypercoagulability and the preventive anticoagulant efficacy of LMWH.

TEG provides a comprehensive real-time functional assessment of the entire coagulation cascade, aiding clinicians in identifying perioperative hypercoagulability. The R value reflects the functional status of thrombin. On postoperative day 1, patients showed a significant decrease in the R value compared to preoperative levels, followed by an increase on postoperative day 3. This indicates that thrombin activity was activated on postoperative day 1, placing patients in a hypercoagulability, which then diminished by the third day. Additionally, the increase in R value on postoperative day 3 was more pronounced in patients who received prophylactic anticoagulation compared to those who did not, suggesting that prophylactic anticoagulation suppressed thrombin activity and helped reduce hypercoagulability to some extent. MA reflects the functional status of platelets, and the gradual increase in MA after surgery indicates progressive platelet activation, which is often an overlooked aspect in clinical practice. Based on the TEG results, thrombin-related hypercoagulability were predominant on postoperative day 1, while platelet-related hypercoagulability became dominant on day 3. This suggests that clinical anticoagulation strategies should be adjusted accordingly, with phase-specific and targeted modifications in antithrombin and antiplatelet therapy [17, 27, 28]. Additionally, using TEG for dynamic monitoring helps assess the effectiveness of antithrombotic therapy, providing clinicians with a reference to adjust drug types and dosages, thereby achieving individualized precision treatment [17, 29].

In this study, we observed that the levels of D-dimer gradually increased after surgery and were closely associated with the occurrence of VTE. Through ROC curve analysis, we evaluated the predictive value of D-dimer for VTE, and the results showed AUCs of 0.732, 0.790, and 0.847 preoperatively, on postoperative day 1, and day 3, respectively. D-dimer is a small molecular fragment derived from the fibrinolysis of cross-linked fibrin during the coagulation and fibrinolysis processes. Elevated levels of D-dimer typically indicate increased fibrinolytic activity in the body and are widely used in the prediction and diagnosis of coagulation disorders, such as VTE [30,31,32,33]. Serum D-dimer testing, with its high sensitivity and relatively lower specificity, has become a commonly used screening tool in clinical practice, particularly valuable for ruling out the risk of VTE [34, 35]. Its high sensitivity allows D-dimer testing to effectively detect increased fibrinolytic activity in the body, aiding clinicians in quickly identifying low-risk patients and reducing the need for unnecessary further testing. In addition, studies have found that patients with persistently elevated D-dimer levels have a 2.6-fold increased risk of VTE recurrence compared to those with normal D-dimer levels. This finding suggests that D-dimer is not only a sensitive indicator for the initial occurrence of VTE but also has significant monitoring value in long-term follow-up. It can help identify patients at high risk of recurrence, providing a basis for further anticoagulant therapy and individualized preventive measures [36,37,38].

The combined application of D-dimer and TEG holds great potential in perioperative VTE prevention. D-dimer provides clinicians with an early warning signal, helping to promptly identify patient populations requiring further evaluation and intervention. Meanwhile, TEG, with its dynamic assessment capabilities of hypercoagulability, complements this early warning mechanism. TEG offers a clear visualization of the patient’s coagulation process, helping to define the specific type of hypercoagulability and providing scientific evidence for clinicians to formulate more personalized anticoagulant therapy plans. Furthermore, TEG can continuously monitor anticoagulant efficacy during treatment, enabling clinicians to adjust therapeutic strategies according to the patient’s coagulation status in a timely manner, thereby enhancing the safety and effectiveness of anticoagulant therapy. The combined application of these two approaches offers more comprehensive support for the early identification, classification, and precise treatment of patients at high risk of VTE.

The limitations of this study are as follows: (1) This study is a single-center study with a small sample size, which may limit the generalizability of the results. Future studies with larger sample sizes and multi-center designs could enhance data representativeness and strengthen the robustness of conclusions. (2) The follow-up period in this study was limited, preventing thorough observation of long-term VTE characteristics in patients. Extending the follow-up period would help to better understand the long-term risk of VTE and provide a basis for developing more effective long-term anticoagulation strategies. (3) Although we monitored perioperative changes in D-dimer and TEG, higher-frequency monitoring or combining additional biomarkers may further improve the accuracy of VTE prediction.

Conclusion

In this study, we found that D-dimer and TEG hold significant value in perioperative VTE prevention. D-dimer, as a sensitive biomarker, helps identify high-risk patients for postoperative VTE. Additionally, TEG is valuable for dynamically monitoring hypercoagulability in patients. By analyzing changes in thrombin and platelet function, TEG allows for a more accurate classification of hypercoagulability, providing a scientific basis for individualized anticoagulation therapy.

Data availability

No datasets were generated or analysed during the current study.

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Author notes

  1. Songping Cui, Ruiheng Jiang and Jiaojie Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China

    Songping Cui, Jing Wang, Bin Hu, Hui Li & Shuo Chen

  2. Department of Thoracic Surgery, Beijing Aerospace General Hospital, Beijing, 100076, China

    Ruiheng Jiang

  3. Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, PR China

    Jiaojie Zhao

  4. Mass General Cancer Center, Mass General Brigham, Harvard Medical School, Boston, USA

    Jing Wang

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Contributions: (I) Conception and design: Hui Li, Shuo Chen; (II) Administrative support: Hui Li, Shuo Chen; (III) Provision of study materials or patients: Hui Li, Shuo Chen, Bin Hu; (IV) Collection and assembly of data: Songping Cui, Ruiheng Jiang, Jiaojie Zhao, Jing Wang; (V) Data analysis and interpretation: Songping Cui, Ruiheng Jiang, Jiaojie Zhao; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Corresponding authors

Correspondence to Hui Li or Shuo Chen.

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Ethical approval

The study adhered to the Declaration of Helsinki (revised in 2013) and received approval from the Ethics Committee of Beijing Chaoyang Hospital (No. 2017-Ke-1).

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Not applicable.

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The authors declare no competing interests.

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Cui, S., Jiang, R., Zhao, J. et al. Thromboelastography-based dynamic evaluation of perioperative coagulation changes and anticoagulant efficacy in lung cancer patients. Thrombosis J 23, 31 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12959-025-00718-8

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12959-025-00718-8

Keywords

Thrombosis Journal

ISSN: 1477-9560

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